Although Parkinson's disease (PD) was first described in 1817, the cause still remains obscure. A large body of experimental evidence indicates that destruction of dopaminergic neurons may result from a series of inter-related mechanisms involving microglial activation, up-regulation of inflammatory mediators, and interactions with oxidative stressors. Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) are potent anti-oxidants and anti-inflammatory compounds that may play an important role in modulating toxic processes associated with oxidative stress and inflammation. The specific aims of this proposed study are to examine whether aspirin and other NSAIDs are associated with a lower risk of PD, and to determine whether inflammation (as indicated by biological markers) may be associated with increased PD risk. To achieve these goals, we propose to analyze existing data from a longitudinal multicenter cohort study, Cardiovascular Health Study, in which information on medication use and physician- diagnosed PD was collected every year among 5,888 subjects 65 years and older since 1989. Inventories of current medications collected yearly during follow-up examinations will be used to assess exposure to prescription and over-the-counter NSAIDs. Six baseline biological markers of inflammation will also be used to assess the presence of inflammation. Relative risk estimates and 95% confidence intervals will be used as measures of association. The proposed study would contribute to our understanding of whether inflammation is associated with an increased risk of PD and whether NSAIDs may represent common medicines that could prevent or reduce the risk of developing PD, thereby reducing the burden of this neurological disease in the population. PUBLIC HEALTH RELEVANCE: Although Parkinson's disease (PD) was first described in 1817, the cause still remains obscure. The proposed study will contribute to our understanding of whether aspirin and similar medications (NSAIDs) may represent common drugs that could prevent or reduce the risk of developing PD, thereby reducing the burden of this neurological disease in the population.